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Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution

Institute of Reproductive Medicine of the University, D-48129 Münster, Germany

Address all correspondence and requests for reprints to: Prof. Dr. E. Nieschlag, F.R.C.P., Institute of Reproductive Medicine of the University, Domagkstr. 11, D-48129 Münster, Germany. E-mail: nieschl{at}uni-muenster.de.

Abstract

The effect of testosterone (T) substitution therapy on blood vessel functions in relation to cardiovascular disease has not been fully elucidated. In 36 newly diagnosed nonsmoking hypogonadal men (37.5 ± 12.7 yr) endothelium-dependent flow-mediated vasodilatation (FMD; decreased in atherosclerosis) of the brachial artery was assessed before treatment and after 3 months of T substitution therapy (250 mg testosterone enanthate im every 2 wk in 19 men, human chorionic gonadotropin sc twice per week in 17 men). Twenty nonsmoking controls matched for age, low-density lipoprotein cholesterol (LDL-C), body height, and baseline diameter of the artery were selected for repeated measurements from a larger eugonadal control group (n = 113). In hypogonadal men, basal FMD (17.9 ± 4.5%) was significantly higher than in the large (11.9 ± 6.4%) and matched control (11.8 ± 7.1%, both P < 0.001) groups. Grouped multiple linear regression analysis revealed a significant negative association of T levels with FMD within the hypogonadal range, but no significant association was seen within the eugonadal range. During substitution therapy, T levels increased from 5.8 ± 2.3 to 17.2 ± 5.1 nmol/liter and FMD decreased significantly to 8.6 ± 3.1% (P < 0.001, analysis for covariance for repeated measurements including matched controls). LDL-C and advanced age contributed significantly to decrease FMD (P = 0.01, P = 0.04, respectively). Because T substitution adversely affects this important predictor of atherosclerosis, other contributing factors (such as smoking, high blood glucose, and LDL-C) should be eliminated or strictly controlled during treatment of hypogonadal men.

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